Neural regulation of water balance is mediated by a circuit that includes circumventricular and forebrain structures. These structures respond to plasma and cerebrospinal fluid hyperosmolality, angiotensin II and input from volume- and baroreceptors. Experiments outlined in this proposal will continue studies that we began five years ago. We will test the hypothesis that the metabolic activity of the subfornical organ, a circumventricular organ, is modified by sensory and humoral inputs and by several neurotransmitters. To test this hypothesis three groups of experiments were designed: (1) we will investigate whether the inputs from baroreceptors alter the functional activity of the subfornical organ in response to peripheral angiotensin II; (2) we will investigate whether the subfornical organ is the primary site of action of angiotensin II; and (3) we will investigate whether the subfornical organ is responsive to different neurotransmitters and whether multiple circuits are activated by them. The primary methodology will involve the autoradiographic (14C) deoxyglucose technique. The first question will be investigated in sino-aortic denervated and sham-operated preparations. The primary site of action of AII will be investigated in preparations in which connections between the subfornical organ and the anteroventral third ventricle (AV3V) area are interruped. Some investigators have indicated that the primary site of AII activation may be the AV3V area. If angiotensin II increases glucose utilization in the subfornical organ of lesioned rats to the same degree as in sham-operated animals, this will indicate that angiotensin II stimulation of the subfornical organ is not dependent on input from AV3V area. Multiplicity of circuits within the subfornical organ subserving drinking behavior will be examined by topically stimulating the subfornical organ with putative neurotransmitters angiotensin II, serotonin, and acetylcholine. Comparison of the patterns of activation of neural structures and behavior by each of these pharmacologic agents will allow us to determine whether there are multiple circuits in the subfornical organ.